Approximately 1.7% of the genes in the human genome encode protein kinases making kinases one of the more abundant classes of enzymes. To date, there are no therapeutic compounds used for any brain disorders, other than brain cancers, that have been developed to purposefully modulate kinase activity despite the implication of kinases as important mediators of a variety of brain functions.
Indolocarbazole alkaloids such as staurosporine and K252a, which are known to target the ATP binding site of kinases, inhibit a variety of kinases in a dose dependent manner. Despite their lack of biochemical selectivity, a number of indolocarbazoles are currently in pre-clinical and clinical development largely for oncology indications, but also for other disease areas such as diabetic macular edema. Synthetic efforts that break the planarity of the indolocarbazole core, such as bisindoylmaleimides, have given rise to inhibitors with improved specificity between families of serine/threonine and tyrosine kinases.